Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis

INTRODUCTION — 

Abnormal uterine bleeding (AUB) refers to uterine bleeding in a nonpregnant person that is abnormal in volume, frequency, duration, and/or regularity [1].

The evaluation of common causes of AUB in adolescents will be discussed here. The management of AUB in adolescents and a more comprehensive discussion of the evaluation of AUB in older reproductive-age persons are presented separately.

●(See "Anovulatory uterine bleeding in adolescents: Management".)

●(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)

NORMAL MENSTRUAL CYCLE — 

The normal menstrual cycle is controlled by a complex feedback system involving the hypothalamus, pituitary, ovary, and uterus (figure 1).

Cycle length, bleeding duration, and blood flow — Menstrual cycles vary considerably during the first few years after menarche due to inconsistent ovulation. Most cycles in adolescents are 21 to 45 days with 2 to 7 days of menstrual bleeding (figure 2) [2-5]. In a systematic review of observational studies describing menstrual patterns during the first year after menarche, the mean cycle length was 34.5 days (range 32 to 61) [6]. Mean bleeding duration ranged from 4.9 to 5.4 days; bleeding of ≥7 days' duration occurred in 2 to 11 percent of cycles.

In contrast, the average adult menstrual cycle lasts 28 days to 35 days with four to six days of menstrual bleeding. The median blood loss during each menstrual period is 30 mL; the upper limit of normal is 80 mL. (See "Normal menstrual cycle".)

Ovulatory cycles — The duration of time that it takes to establish regular ovulatory cycles increases with increasing age at the time of menarche [6-8]. One-half of cycles are ovulatory by one year in those with menarche at <12 years, by three years when menarche occurs between 12 and 13 years, and by 4.5 years when menarche occurs at ≥13 years [7].

In the first one to two years after menarche, all adolescents may experience anovulatory cycles in which the endometrium lacks the stabilizing effect of progesterone. In such cycles, the endometrium becomes excessively thickened and can break down and slough off when estrogen is withdrawn (estrogen-withdrawal bleeding) or when it becomes unstable (estrogen-breakthrough bleeding) [9].

When regular, ovulatory cycles do occur, they are associated with increased progesterone secretion, which helps to stabilize endometrial growth and permits more complete shedding [10].

Adolescents who continue with irregular menses and anovulatory bleeding appear to have delayed maturation or dysfunction of the hypothalamic-pituitary-ovarian axis. In these adolescents, the midcycle surge of luteinizing hormone does not occur and estrogen secretion is sustained in the absence of progesterone and ovulation [10,11]. The endometrium proliferates beyond the ability of estrogen to maintain it. Irregular, heavy bleeding occurs when the endometrium becomes unstable (estrogen-breakthrough bleeding) and continues until estrogen-induced repair takes place [9].

ABNORMAL UTERINE BLEEDING

Clinical features — AUB refers to menstrual bleeding that occurs outside the normal range and includes any of the following [1,2,12]:

●Absence of menses (amenorrhea)

●Menses at irregular intervals

●Menstrual period intervals <every 21 days or >every 45 days [2]

●Menses that are excessive in duration (ie, >7 days)

●Heavy menstrual bleeding, defined subjectively as a volume of menstrual flow that interferes with quality of life (physical, emotional, social, and/or material) [1,13]

●Intermenstrual or breakthrough bleeding

"Anovulatory uterine bleeding" is the preferred term for heavy noncyclic uterine bleeding unrelated to structural lesions of the uterus, systemic disease, or sexually transmitted infection [14]. Clinical features suggestive of anovulatory uterine bleeding include irregular periods and the absence of premenstrual symptoms (eg, breast tenderness, bloating, mood swings, or uterine cramping).

This pattern of bleeding was previously called "dysfunctional uterine bleeding." In the International Federation of Gynecology and Obstetrics classification system, anovulatory uterine bleeding is classified as a type of ovulatory dysfunction [15].

Source of abnormal uterine bleeding — Adolescents with AUB typically present with a complaint of "abnormal vaginal bleeding." The uterus is the most common source of vaginal bleeding (table 1). Other sources include the ovary, cervix, vagina, vulva, gastrointestinal tract, and urinary tract. Nonuterine sources of vaginal bleeding are discussed separately. (See "Causes of female genital tract bleeding" and "Evaluation of vulvovaginal bleeding in children and adolescents".)

Heavy bleeding is typically from the uterus, whereas light bleeding, staining, or spotting may be from any site along the genital tract. Postcoital bleeding suggests bleeding from the cervix or other lower genital tract source. Bleeding that occurs solely with urination or defecation suggests a urinary or gastrointestinal source. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on 'Gynecologic and obstetric history'.)

CLINICAL EVALUATION

Triage and severity assessment — Initial triage of the adolescent with suspected AUB includes assessment of hemodynamic stability and pregnancy status, which influence disposition, differential diagnosis, and further evaluation.

●Patients who are hemodynamically unstable (eg, tachycardic, hypotensive, orthostatic) should be referred/transported to the emergency department for stabilization and hospitalization before proceeding with additional evaluation.

Blood should be obtained for cross-matching in the event transfusion is necessary. Blood for evaluation of bleeding disorders should also be obtained prior to administration of blood products or estrogen because these can cause inaccurate results. However, this should not delay transfusion if the patient is unstable. (See 'Heavy menstrual bleeding' below.)

●Patients who are hemodynamically stable can be further evaluated in the outpatient setting.

●If the urine pregnancy test is positive, pregnancy can be confirmed with a serum beta-human chorionic gonadotropin (hCG) level and the etiology evaluated with ultrasonography. Vaginal bleeding with pregnancy may be a result of:

•Pregnancy loss (see "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology")

•Ectopic pregnancy (see "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation')

•Molar pregnancy (see "Hydatidiform mole: Epidemiology, clinical features, and diagnosis", section on 'Diagnostic evaluation')

Additional causes of vaginal bleeding in pregnant patients are discussed separately. (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

●If the urine pregnancy test is negative, the patient is evaluated for nonpregnancy-related causes of AUB.

History — The history (table 2) should be obtained both with and without the patient's caregiver present. The caregiver may be more precise about menstrual patterns and may share details that the patient would omit. In addition, adolescents may be more comfortable discussing menstruation if a caregiver is present. Speaking with the patient alone maintains their confidentiality on subjects that they may be uncomfortable discussing in front of their caregiver (eg, sexual activity, sexual abuse). (See "Confidentiality in adolescent health care", section on 'Overview'.)

●Menstrual history – It is important to obtain as much information as possible about the menstrual history, including age of menarche, menstrual pattern, associated symptoms, and events that coincided with a change in the menstrual pattern (if there has been a change) (table 2) [3].

We ask patients with irregular cycles to maintain a menstrual calendar, either on paper (figure 3) or using one of several freely available smart phone applications [16].

Heavy menstrual bleeding is defined clinically as bleeding that interferes with activities and/or physical, emotional, social, and/or material quality of life [1,13]. Quantification of blood flow is challenging at best and is complicated by the large variety of menstrual products on the market as well as the effect of school limitations and hygiene preferences on the quantity of sanitary products used.

•Although it is important to try to quantify the volume of menstrual blood flow in adolescents who report heavy menstrual flow, neither patients nor clinicians can accurately do so [17,18]. In addition, there is little correlation between the number of sanitary pads or tampons used and actual menstrual blood loss [19]. Nonetheless, the history should include the type/size of pad or tampon used, the number of pads or tampons used per day (or the hours each item is worn) [20], and an estimate of the degree to which the pad or tampon is soaked [21].

•In the absence of other means to measure blood loss, the clinician must rely upon indirect indicators of heavy flow, such as passing blood clots larger than 2.5 cm (1 inch) in diameter, bleeding through clothes, the need to change sanitary protection during the night, signs or symptoms of volume depletion during the menstrual period, and measurement of hemoglobin or hematocrit (table 3) [22-24]. (See 'Initial laboratory evaluation' below.)

•A semiquantitative tool, the pictorial blood loss assessment chart (PBAC), has been developed to estimate menstrual bleeding volume (figure 4). A PBAC score is calculated from the number of pads or tampons used, the degree to which each is saturated, and the passage of blood clots [25]. A score of ≥100 has been correlated with heavy menstrual bleeding [25,26]. In an observational study, PBAC scores correlated with adolescents' self-report of "heavy," "medium" (normal), and "light" menstrual flow; additional studies are necessary to confirm the findings and determine the appropriate cutoff value for adolescents [27].

●Sexual history – The sexual history should be obtained without the caregiver present. History should include: information regarding contraception and condom use; number of partners; new partners; history of sexually transmitted infections (STIs) or current symptoms (eg, vaginal discharge, pelvic pain, bleeding with intercourse); previous pregnancy or abortion; whether sexual activity was forced or consensual; and whether the adolescent has a history of sexual abuse or assault (table 2) [3,9,28]. (See "Screening for sexually transmitted infections", section on 'Sexual history'.)

●Past medical history – The past medical history should include information about (table 2) [3,11]:

•Systemic illness, including hematologic or kidney disease or gastrointestinal bleeding

•Current or recent medications (including over-the-counter medications and complementary/alternative agents); ask specifically about:

-Contraceptive use and method (some forms may cause irregular bleeding)

-Nonsteroidal anti-inflammatory drugs, including aspirin, and aspirin-containing over-the-counter medications (anticoagulation effects); antiplatelet medications can precipitate bleeding that may not have occurred otherwise in patients with von Willebrand disease (see "Approach to the child with bleeding symptoms", section on 'Medications' and "Clinical presentation and diagnosis of von Willebrand disease", section on 'Clinical features')

-Valproic acid (anticoagulation effects)

-Antidepressants and antipsychotics (may affect the hypothalamic-pituitary-ovarian [HPO] axis)

●Review of systems – The review of systems should include information about weight change (loss or gain), fatigue, self-induced vomiting as a means of weight control, disordered eating behaviors, hirsutism, acne, visual changes, headaches, galactorrhea, change in bowel habits, and abdominal pain (table 2) [29]. Unexplained weight changes, palpitations, heat or cold intolerance, and/or changes in hair, skin, or nails may indicate thyroid dysfunction or malnutrition [3]. Bleeding that occurs solely with urination or defecation suggests a urinary or gastrointestinal source. Deteriorations in mood and anxiety symptoms may indicate psychosocial disruption severe enough to impact HPO axis functioning. Presence of severe acne and/or hirsutism may indicate hyperandrogenism and/or polycystic ovary syndrome (PCOS).

Adolescents with complaints of heavy menstrual flow should be asked about bleeding from other sites (easy bruising, epistaxis, gingival bleeding, postoperative bleeding) and symptoms of acute or chronic anemia (lightheadedness, fatigue, syncope, weakness, headache) [3,9,11,30].

●Social history – The social history should include information about family and social stressors, substance use, exercise patterns, and athletic participation (eg, intensity of exercise and training). Asking questions about menstrual-related school absence or decreased participation in recreational activities (eg, sports, hobbies) may provide information about the effects of menses on quality of life [11].

●Family history – The family history should include information about bleeding disorders, infertility, menstrual disorders, thyroid disease, and any cancers of the reproductive organs [3,31,32]. A strong family history of diabetes mellitus, infertility, and/or disorders of lipids or triglycerides may be suggestive of PCOS. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome (PCOS) in adolescents".)

Physical examination — Information from the physical examination may help to narrow the diagnostic possibilities and target subsequent laboratory or radiographic evaluation (table 4).

●General examination – The general examination should include (table 4) [3,11,31]:

•Measurement of height, weight, and body mass index with attention to trends from previous growth patterns, if available

•Visual assessment of body habitus and fat distribution (eg, Cushing syndrome, Turner syndrome)

•Vital signs, including orthostatic vital signs (if bleeding is acute, prolonged, and/or heavy)

•Palpation of the thyroid gland for enlargement or other abnormalities

•Signs of androgen excess (eg, hirsutism, acne, male-pattern balding) to evaluate for PCOS (see "Diagnostic evaluation of polycystic ovary syndrome (PCOS) in adolescents", section on 'History and physical examination')

•Evidence of easy bruising or oozing gums to evaluate for a bleeding disorder

•Visual field testing to evaluate the possibility of a pituitary tumor

•Assessment of lymph nodes (lymphadenopathy may be a sign of malignancy)

•Sexual maturity rating of the breasts (picture 1) and assessment for galactorrhea. Breast development provides evidence of estrogenization

•Examination of the hair and skin for thinning hair, dry skin, excessive sweating, acanthosis nigricans, or signs of abnormal bleeding (eg, petechiae and/or bruising) should be noted, particularly in patients with heavy menstrual bleeding

•Palpation of the abdomen (pregnancy, uterine mass, ovarian mass)

●External genitalia – Examination of external genitalia includes evaluation of clitoral size, sexual maturity rating for pubic hair development (picture 2), and the hymen (figure 5).

It is also important to look for extrauterine sources of bleeding (eg, perineal trauma, vulvar lesions, signs of STIs). Adolescents assigned female at birth who have signs of perineal trauma should be questioned privately about sexual abuse or assault. (See "Sexually transmitted infections: Issues specific to adolescents", section on 'STI clinical patterns' and "Evaluation of sexual abuse in children and adolescents".)

●Pelvic examination – Pelvic examination may be distressing for adolescents, especially those who are not sexually active. Unless the bleeding is severe, the pelvic and rectal examination may be postponed pending a trial of medical therapy, if such therapy is warranted. (See "Anovulatory uterine bleeding in adolescents: Management" and "Congenital anomalies of the hymen and vagina".)

When warranted, many adolescents can tolerate a one finger digital examination (provided the hymenal opening is wide enough to admit the finger [33]) to assess the depth of the vagina and the presence and normality of the cervix, uterus, and ovaries. However, this should only be attempted if the patient shows signs of estrogenization (eg, breast development, vulvovaginal mucous). Otherwise, a digital examination will be very painful.

Many adolescents are also able to tolerate a speculum examination with an appropriate size speculum to look for abnormalities (eg, polyps, vaginal lacerations).

Pelvic examination under anesthesia may be necessary if pelvic examination is inadequate or an appropriate diagnosis cannot be established despite imaging.

Initial laboratory evaluation — Our initial laboratory evaluation for adolescents who present with AUB generally includes:

●Pregnancy test (if not already performed)

●Complete blood count

●Measurement of thyroid-stimulating hormone

●Screening for STIs if sexually active (see "Screening for sexually transmitted infections", section on 'Females')

It is essential to obtain a urine pregnancy test in adolescents who present with unexplained vaginal bleeding, regardless of the stated sexual history; adolescents may be unwilling to disclose sexual activity for a variety of reasons. (See 'Pregnancy' below.)

Prolactin measurement may also be warranted, particularly in females with headaches or nipple and/or breast complaints (eg, galactorrhea). (See "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Clinical presentation'.)

Additional laboratory evaluation for adolescents with AUB depends upon the pattern of bleeding and findings from the history and physical examination. (See 'Approach to diagnosis' below.)

Indications for pelvic ultrasonography — Pelvic ultrasonography can provide useful information about genital tract anatomy and detect structural abnormalities of the cervix, uterus, and ovaries. Although an intravaginal ultrasound provides more detail, a transabdominal ultrasound is often more appropriate for adolescent patients. This method should be used when a patient is uncomfortable with or cannot tolerate an intravaginal probe.

Relevant findings on pelvic ultrasonography may include:

●Vaginal or cervical outlet obstruction in patients with cyclic pain (see "Congenital anomalies of the hymen and vagina" and "Benign cervical lesions and congenital anomalies of the cervix")

●Leiomyomas (fibroids) (see "Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history", section on 'Diagnostic evaluation')

●Ovarian masses (see "Ovarian cysts in infants, children, and adolescents")

●Multiple follicles around the periphery of the ovary (may indicate PCOS) (see "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome (PCOS) in adolescents", section on 'Differential diagnosis')

PREGNANCY — 

Pregnancy and pregnancy-related problems are a common cause of uterine bleeding in adolescents and may be life threatening.

●If the urine pregnancy test is positive, serum quantitative beta-human chorionic gonadotropin (hCG) and/or pelvic ultrasonography should be included in the evaluation. Vaginal bleeding with pregnancy may be a result of:

•Pregnancy loss (see "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology")

•Ectopic pregnancy (see "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation')

•Molar pregnancy (see "Hydatidiform mole: Epidemiology, clinical features, and diagnosis", section on 'Diagnostic evaluation')

Additional causes of vaginal bleeding in pregnant patients are discussed separately. (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

CLASSIFY THE BLEEDING PATTERN — 

Information from the clinical evaluation is used to classify nonpregnant adolescents with abnormal vaginal bleeding into one of the following patterns (table 5) [15]:

●Amenorrhea (absence of menses).

●Irregular bleeding (unpredictable intervals between episodes of menstrual bleeding).

●Prolonged and/or heavy menstrual bleeding.

•Prolonged menstrual bleeding lasts >7 days.

●Heavy menstrual bleeding is defined clinically as interfering with activities and/or quality of life (physical, emotional, social, and/or material) [1,13]. Soaking a sanitary pad or tampon more frequently than every two hours is a useful rule of thumb but is subject to each person's definition of soaking. (See 'History' above.)

●Intermenstrual bleeding (bleeding between well-defined cyclical menses).

Although this categorization narrows the differential diagnosis and determines the need for additional testing (table 5), it may be difficult to classify the abnormal menstrual bleeding into one particular pattern for a number of reasons. Menstrual cycles can vary substantially in the first year or two after menarche, and the distinction between regular and irregular cycles is not always clear. The categories may overlap (eg, irregular bleeding can also be heavy), and causative conditions may have more than one pattern or present atypically.

APPROACH TO DIAGNOSIS — 

The most common cause of AUB in adolescents during the initial one to two years of menstruation is anovulatory cycles, which are related to immaturity of the hypothalamic-pituitary-ovarian (HPO) axis. However, an immature HPO axis is always a diagnosis of exclusion [3,11,34]. Other common causes of AUB in adolescents include pregnancy/pregnancy-related problems, bleeding disorders (including bleeding related to systemic disease), polycystic ovary syndrome (PCOS), thyroid dysfunction, hypothalamic dysfunction (eg, related to stress, exercise, underweight, acute weight loss, or obesity), hormonal or intrauterine contraception, and infection (table 1). More than one cause may contribute to or exacerbate AUB in a given adolescent.

Amenorrhea — Amenorrhea is the absence of menses. Amenorrhea may be primary (absence of menarche by age 15 years) or secondary (absence of menses for ≥90 days in adolescents who previously had regular menstrual cycles or >6 months in those who had irregular menses).

The laboratory evaluation should include:

●A urine or serum qualitative beta-human chorionic gonadotropin (hCG), if not already performed, to exclude pregnancy (see "Pregnancy in adolescents", section on 'Diagnosis of pregnancy')

●Thyroid-stimulating hormone (TSH), if not already performed, to evaluate for hypothyroidism

●Prolactin level to assess for a prolactinoma

●Follicle-stimulating hormone (FSH) to assess for premature ovarian insufficiency

●Total testosterone, 17-hydroxyprogesterone (17-OHP), and dehydroepiandrosterone sulfate (DHEA-S) if there are signs of hyperandrogenism (see 'Menarche occurred <12 months ago and <6 previously regular cycles' below)

Hypothalamic dysfunction related to exercise, psychological stress, malnutrition, chronic disease, acute weight loss, or obesity may also cause amenorrhea. Other causes of amenorrhea and the evaluation and management of primary and secondary amenorrhea are discussed separately. (See "Causes of primary amenorrhea" and "Evaluation and management of primary amenorrhea" and "Epidemiology and causes of secondary amenorrhea" and "Evaluation and management of secondary amenorrhea".)

Irregular bleeding — Irregular bleeding refers to unpredictable intervals between episodes of menstrual bleeding. Irregular bleeding may co-occur with prolonged and/or heavy bleeding.

Menarche occurred <12 months ago and <6 previously regular cycles

●Obtain urine pregnancy test, if not already done.

●If menses are also heavy or prolonged, conduct additional evaluation for heavy menstrual bleeding. (See 'Heavy menstrual bleeding' below.)

●Patient with signs, symptoms, or risk factors for hyperprolactinemia – Check prolactin level if medications include an antipsychotic or other agent that causes hyperprolactinemia (table 6), patient is using cannabis, or patient has prominent headache, visual field abnormality, papilledema, or galactorrhea. (See "Causes of hyperprolactinemia".)

•If prolactin level ≥100 ng/mL, obtain magnetic resonance imaging (MRI) of brain to look for tumor.

•If prolactin level >30 and <100 ng/mL, repeat level in the morning and, if it remains elevated, refer to an endocrinologist for further evaluation.

●If patient is hirsute, has severe acne, or has signs of virilization, check androgen levels:

•Total testosterone.

-If total testosterone ≥150 ng/dL, we obtain a pelvic ultrasound to look for an ovarian tumor and adrenal computed tomography (CT) to look for an adrenal tumor.

-If total testosterone <150 and >60 ng/dL, we evaluate for PCOS. (See "Diagnostic evaluation of polycystic ovary syndrome (PCOS) in adolescents".)

Other experts, including the American College of Obstetricians and Gynecologists (ACOG), use a higher threshold (200 ng/dL) [35].

•17-OHP – If 17-OHP >200 ng/dL, refer to an endocrinologist for further evaluation and treatment of probable nonclassic congenital adrenal hyperplasia (NCCAH). When possible, 17-OHP should be drawn between 7 and 9 AM. If a level is drawn later in the day, repeat levels should be repeated between 7 and 9 AM to confirm absence of NCCAH. (See "Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents".)

•DHEA-S – If DHEA-S >700 mcg/dL, obtain adrenal CT to look for an adrenal tumor.

●Patient is sexually active – Examine the external genitalia and send swabs or urine to test for sexually transmitted infections (STIs) of the vulva, vagina, and cervix, which may cause intermenstrual bleeding that appears to be irregular. (See 'Intermenstrual bleeding in patients with regular menses' below.)

If the above evaluation does not reveal an etiology, the patient likely has an immature HPO axis, which causes anovulatory bleeding and is the most common cause of irregular bleeding during the first two years after menarche [3,34,36]. (See 'Ovulatory cycles' above.)

Patients should continue to be monitored, and if irregular bleeding persists for more than two years, they should have additional laboratory evaluation. (See 'Menarche occurred >12 months ago or >6 previously regular cycles' below.)

If additional laboratory test results are normal, the patient may have hypothalamic dysfunction. This is another cause of ovulatory dysfunction secondary to excessive exercise, stress, or changes in body weight.

Menarche occurred >12 months ago or >6 previously regular cycles

●Obtain urine pregnancy test, if not already done.

●Prolactin level (if not already obtained).

•If prolactin level ≥100 ng/L, obtain MRI of brain to look for tumor.

•If prolactin level >30 and <100 ng/mL, repeat level in the morning and, if it remains elevated, refer to an endocrinologist for further evaluation.

●TSH (if not already obtained) – An elevated TSH suggests hypothyroidism, and a low TSH suggests hyperthyroidism. (See "Acquired hypothyroidism in childhood and adolescence", section on 'Diagnosis' and "Clinical manifestations and diagnosis of Graves disease in children and adolescents", section on 'Diagnostic evaluation'.)

•If TSH is low, refer to an endocrinologist for further evaluation and treatment.

•If TSH is elevated, check free T4.

-If free T4 is normal, recheck TSH and free T4 in one to two months.

-If free T4 is low, check thyroid antibodies (antithyroperoxidase and antithyroglobulin) and start levothyroxine or refer to an endocrinologist if not comfortable prescribing levothyroxine. (See "Acquired hypothyroidism in childhood and adolescence", section on 'Diagnosis' and "Clinical manifestations and diagnosis of Graves disease in children and adolescents", section on 'Diagnostic evaluation'.)

●FSH – If FSH is elevated, refer to an endocrinologist/adolescent medicine specialist/pediatric and adolescent gynecologist for further evaluation and treatment of ovarian insufficiency.

●Patient is hirsute, has severe acne, or signs of virilization, check androgen levels (if not already obtained):

•Total testosterone.

-If total testosterone ≥150 ng/dL, we obtain pelvic ultrasound to look for ovarian tumor and adrenal CT to look for an adrenal tumor.

-If total testosterone >60 and <150 ng/dL, we evaluate for polycystic ovary syndrome (PCOS). (See "Diagnostic evaluation of polycystic ovary syndrome (PCOS) in adolescents".)

Other experts, including the ACOG, use a higher threshold (200 ng/dL) [35].

•17-OHP – If 17-OHP >200 ng/dL, refer to an endocrinologist for further evaluation and treatment of probable NCCAH. When possible, 17-OHP should be drawn between 7 and 9 AM. If a level is drawn later in the day and is normal, a repeat level should be drawn between 7 and 9 AM to confirm the absence of NCCAH. (See "Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents".)

•DHEA-S – If DHEA-S >700 mcg/dL, obtain adrenal CT to look for an adrenal tumor.

●Patient is sexually active – Examine the external genitalia and send swabs or urine to test for STIs of the vulva, vagina, and cervix, which may cause intermenstrual bleeding that appears to be irregular. (See 'Intermenstrual bleeding in patients with regular menses' below.)

If all laboratory test results are normal, the patient may have hypothalamic dysfunction. This is another cause of ovulatory dysfunction secondary to excessive exercise, stress, or changes in body weight.

Heavy menstrual bleeding — In adolescents, heavy menstrual bleeding typically occurs at irregular intervals, indicating that it is anovulatory. (See 'Irregular bleeding' above.)

Heavy menstrual bleeding that occurs at regular intervals or at the onset of menses often is caused by a bleeding disorder [37-41]. Less commonly, heavy menstrual bleeding may be caused by systemic illness or structural lesions [38,42].

●Extremely heavy bleeding at regular intervals or at onset of menses – We consider the possibility of a bleeding disorder (coagulation factor deficiency or inherited or acquired platelet disorder) in adolescents who present with extremely heavy flow during their first menses, bleeding requiring blood transfusion or hospitalization, and patients with refractory heavy menstrual bleeding and concomitant anemia. Consultation with a hematologist is warranted if a bleeding disorder is suspected or diagnosed [43,44].

Bleeding disorders among adolescents with heavy menstrual bleeding include, but are not limited to [37-39,41,45-48]:

•von Willebrand disease (see "Clinical presentation and diagnosis of von Willebrand disease" and "von Willebrand disease (VWD): Gynecologic and obstetric considerations")

•Factor VII deficiency (see "Rare inherited coagulation disorders")

•Immune thrombocytopenia (see "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis")

•Platelet dysfunction (see "Inherited platelet function disorders (IPFDs)")

•Thrombocytopenia secondary to malignancy or treatment for malignancy (ie, chemotherapy or hematopoietic stem cell transplantation) (see "Causes of thrombocytopenia in children")

Among these, von Willebrand disease is most common. In a systematic review of 11 studies including 988 adults presenting with heavy menstrual bleeding, the prevalence of von Willebrand disease was 13 percent [49].

In retrospective studies in adolescents hospitalized for heavy menstrual bleeding, the prevalence of bleeding disorders ranges from 5 to 28 percent [38-40,42,46]. In observational studies with adolescents who were evaluated in a hematology or multidisciplinary clinic for heavy menstrual bleeding, the prevalence of bleeding disorders was approximately 20 to 60 percent [41,47,48,50-52].

The minimum laboratory evaluation for bleeding disorder in adolescents with heavy menstrual bleeding should include [12,43,53] (see "Approach to the child with bleeding symptoms", section on 'Initial laboratory evaluation'):

•Complete blood count, if not already performed, to evaluate for anemia, thrombocytopenia, and hematologic malignancies such as leukemia

•Ferritin, iron, and total iron-binding capacity to evaluate for iron deficiency without anemia [54]

•Coagulation panel (activated partial thromboplastin time/partial thromboplastin time, prothrombin time, and fibrinogen)

The evaluation generally also includes a von Willebrand panel [3,53,55,56]:

•Plasma von Willebrand factor (VWF) antigen

•Plasma VWF activity (ristocetin cofactor activity)

•Factor VIII activity

The von Willebrand panel should be obtained at the time of presentation (prior to transfusion and administration of estrogen products) or after exogenous estrogen has been discontinued for seven days. Exogenous estrogen may increase the production of VWF, resulting in falsely normal values [57].

Consultation with a hematologist is suggested if any abnormalities are detected on the von Willebrand panel. (See "Clinical presentation and diagnosis of von Willebrand disease".)

●Other patients with heavy bleeding – In adolescents with heavy menstrual bleeding in whom a bleeding disorder is unlikely or has been excluded, additional evaluation includes:

•Review of medication list for agents that cause bleeding (eg, anticoagulants, platelet inhibitors, nonsteroidal anti-inflammatory drugs including aspirin)

•Complete blood count, if not already performed

•Measurement of serum TSH to evaluate thyroid function (if not already performed)

•Measurement of C-reactive protein, erythrocyte sedimentation rate, glycosylated hemoglobin, and kidney and liver function tests to evaluate for chronic disease or systemic disease, as warranted by the history (table 2) and physical examination (table 4)

•Pelvic ultrasonography (if it has not already been performed) to assess for structural causes, such as leiomyomas (fibroids), polyps, and/or ovarian tumors (see 'Indications for pelvic ultrasonography' above)

Heavy bleeding may also be a symptom of Ehlers-Danlos syndrome (EDS). In patients with joint hypermobility and other symptoms consistent with a connective tissue disorder, EDS should be considered. (See "Clinical manifestations and diagnosis of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder", section on 'Other common symptoms and comorbidities'.)

Intermenstrual bleeding in patients with regular menses

●Hormonal contraception and intrauterine devices – Intermenstrual bleeding is a common side effect of oral contraceptives, depot medroxyprogesterone acetate, the contraceptive patch, the vaginal ring, the contraceptive implant, and intrauterine devices. Intermenstrual bleeding also may occur if hormonal contraception is not taken as prescribed. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception" and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Unscheduled bleeding'.)

Before attributing intermenstrual bleeding to contraception, the possibility of pregnancy, cervicitis, or endometrial/cervical pathology must be considered and excluded by examination and/or appropriate laboratory tests. These include a pregnancy test, chlamydia and gonorrhea tests, and evaluation of the pelvis via pelvic examination and/or pelvic imaging.

●STI – STIs may cause intermenstrual bleeding in sexually active adolescents and/or those who have been sexually abused or assaulted. Such patients who have acute vaginal bleeding unrelated to menses should be assessed for cervicitis and upper genital tract infection.

We send urine or swabs for nucleic acid amplification testing to evaluate for Chlamydia trachomatis and Neisseria gonorrhoeae. We also perform a speculum and bimanual examination, with or without pelvic imaging, if indicated by new-onset abdominal or pelvic pain, fever, or other symptoms that suggest elevated risk for pelvic inflammatory disease. (See "Sexually transmitted infections: Issues specific to adolescents" and "Pelvic inflammatory disease: Clinical manifestations and diagnosis".)

●Other causes – Extrauterine gynecologic causes of intermittent bleeding that may mimic abnormal uterine bleeding include:

•Certain medications (eg, anticoagulants, valproic acid)

•Cervical polyps (see "Benign cervical lesions and congenital anomalies of the cervix", section on 'Polyps')

•Cervical ectropion (eversion of the endocervix) (see "Benign cervical lesions and congenital anomalies of the cervix", section on 'Ectropion')

•Foreign bodies (retained tampons are most common among adolescents)

•Trauma (see "Evaluation of sexual abuse in children and adolescents" and "Evaluation and management of adult and adolescent sexual assault victims in the emergency department")

Consultation with an adolescent medicine specialist or pediatric and adolescent gynecologist is merited to further explore these etiologies if the provider is not comfortable with their pelvic examination skills or unsure of when to perform a pelvic examination.

Less common causes of nonuterine genital tract bleeding in adolescents are discussed separately. (See "Causes of female genital tract bleeding".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Absent or irregular periods (The Basics)" and "Patient education: Heavy periods (The Basics)")

●Beyond the Basics topics (see "Patient education: Absent or irregular periods (Beyond the Basics)" and "Patient education: Abnormal uterine bleeding (Beyond the Basics)" and "Patient education: Heavy periods (Beyond the Basics)")

PATIENT PERSPECTIVE TOPIC — 

Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: von Willebrand disease".)

SUMMARY AND RECOMMENDATIONS

●Terminology – Abnormal uterine bleeding (AUB) refers to menstrual bleeding that occurs outside the normal range and includes absence of menses (amenorrhea), menses at irregular intervals (irregular bleeding), heavy flow (heavy menstrual bleeding), and intermenstrual bleeding between regular menses.

"Anovulatory uterine bleeding" is the preferred term for heavy noncyclic uterine bleeding unrelated to structural lesions of the uterus or systemic disease. (See 'Abnormal uterine bleeding' above.)

●Causes – Adolescents with AUB typically present with a complaint of abnormal "vaginal bleeding." The uterus is the most likely source of vaginal bleeding (table 1). Anovulatory uterine bleeding related to immaturity of the hypothalamic-pituitary-ovarian (HPO) axis is the most common cause of AUB in nonpregnant adolescents in the first one or two years after menarche. (See 'Source of abnormal uterine bleeding' above.)

●Triage – Initial triage of the adolescent with suspected abnormal uterine bleeding includes assessment of hemodynamic stability and pregnancy status. (See 'Triage and severity assessment' above.)

•Patients who are hemodynamically unstable (eg, tachycardic, hypotensive, orthostatic) should be referred/transported to the emergency department for stabilization and hospitalization before proceeding with additional evaluation.

•Urine pregnancy test is essential, regardless of the stated sexual history. Pregnancy and pregnancy-related problems commonly cause uterine bleeding in adolescents and may be life-threatening (eg, ectopic pregnancy, pregnancy loss). (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

●Approach to diagnosis – In the nonpregnant adolescent with AUB, the history (table 2), examination (table 4), and initial laboratory evaluation focus on clinical features associated with specific causes and identification of the predominant bleeding pattern, which determines additional evaluation (table 5).

•Amenorrhea – Pregnancy is a common cause of amenorrhea in reproductive-age females. The approach to amenorrhea is discussed separately. (See "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)

•Irregular bleeding – Immaturity of the HPO axis with anovulatory cycles is the most common cause of irregular bleeding in nonpregnant adolescents during the first one to two years after menarche. Hypothalamic dysfunction related to exercise, stress, or changes in body weight can also cause ovulatory dysfunction.

Other causes of irregular bleeding include ovarian insufficiency, thyroid disorders, and hyperprolactinemia, which are evaluated with a follicle-stimulating hormone, thyroid-stimulating hormone (TSH), and prolactin, respectively. If signs or symptoms of hyperandrogenism are present, then ovarian tumor, nonclassic congenital adrenal hyperplasia, and adrenal tumor are evaluated with testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate levels, respectively.

•Prolonged and/or heavy menstrual bleeding – Bleeding disorders (eg, von Willebrand disease) are a common cause of prolonged and/or heavy menstrual bleeding in nonpregnant adolescents with regular menses. Adolescents with heavy flow starting with the first menses, bleeding requiring blood transfusion, or bleeding with associated anemia that does not respond to hormonal therapy should be evaluated for a bleeding disorder.

Other causes include thyroid disorders which are evaluated with a TSH; chronic or systemic disease, which is evaluated with C-reactive protein, erythrocyte sedimentation rate, glycosylated hemoglobin, and kidney and liver function tests; structural abnormalities of uterus and cervix, which are evaluated with a pelvic ultrasound; and certain medications. (See 'Heavy menstrual bleeding' above.)

•Intermenstrual bleeding with regular menses – Causes of intermenstrual bleeding in adolescents include use of hormonal contraception or intrauterine devices, sexually transmitted infections, and extrauterine causes of intermittent bleeding that mimic intermenstrual uterine bleeding.

ACKNOWLEDGMENT — 

The editorial staff at UpToDate, Inc. acknowledge Dr. Robert Zurawin, MD, who contributed to an earlier version of this topic review.